Over the past two decades, Human Immunodeficiency Virus (HIV) has become a chronic condition rather than a fatal disease). This is attributable to use of antiretroviral therapy (ART) which has increased life expectancy of HIV infected individuals. Newer treatment options like tenofovir (TDF) containing ART with simpler once-a-day dosing regimens promise even further increases in survival. A number of studies have however demonstrated accelerated Bone Mineral Density (BMD) loss, higher rates of osteopenia and osteoporosis, and subsequent fractures among HIV-infected individuals compared to the general population. It is not yet known how much of the BMD loss among HIV infected patients is due to HIV infection per se and how much can be attributed to the consequences of ART. Of the different anti-retroviral drugs, the potential effect of tenofovir (TDF) is particularly concerning. Among women of reproductive age, the choice of contraception may also impact bone health. Depot medroxyprogesterone acetate (DMPA, Depo Provera), a widely used progesterone-based contraceptive method has also been associated with reduced BMD. Since DMPA and TDF appear to be independently associated with reduced BMD, this raises concerns that concurrent use of these two agents may potentiate each other's effect and lead to increased long term risk of morbidity related to early osteoporosis and fragility fractures among HIV infected women in resource limited settings. To date, no studies have examined the combined effect of TDF and DMPA. To address this gap, we propose to study the combined effect of DMPA and TDF on BMD over a two year period among young Ugandan women aged 18 to 30 years attending HIV care centers and general health facilities in and around Kampala, Uganda. In addition, the project will determine whether BMD loss and bone turnover with TDF ART initiation over a 2 year follow-up period, is greater with concomitant use of DMPA. The primary outcome will be percent change from baseline in lumbar spine BMD which will be measured at baseline, 6, 12, 18, and 24 months using dual energy x-ray absorptiometry. Project results are expected to contribute novel and important clinically relevant information about BMD loss in a vulnerable population of young HIV infected African women concurrently using DMPA and TDF based ART. The study has potential to inform policy on ART treatment and contraceptive guidelines for HIV infected women particularly in resource limited settings. Results will also form the basis for future studies on safer contraception for infected women on ART, as well as studies on proactive interventions like vitamin D and calcium supplementation that may minimize risk of bone loss.